Screening for cyclooxygenase 2 inhibitors from natural compounds of Radix Glycyrrhizae using computer simulation

Objective: To explore the molecular basis of the effects of Gancao (Radix Glycyrrhizae, GC) on inflammation through the inhibition of cyclooxygenase 2 (COX2). Methods: The Discovery Studio 4.5 System was used to predict the physicochemical properties of GC molecular compounds. The Ligand Profiler was used to screen for natural GC components that could combine with the COX2 pharmacophores. The AutoDock Vina 1.1.2 software was used for the molecular docking of the natural GC components with the COX2 protein. Results: The aromatics were the closest to the nonsteroidal antiinflammatory drugs in terms of the three properties, namely molecular weight, molecular surface area, and molecular solubility, followed by the flavonoids; whereas the terpenoids/saponins differed most from the nonsteroidal antiinflammatory drugs in terms of the three properties; and the aliphatics were inconsistent. One hundred and eighteen small molecules were obtained through the pharmacophore screening using GC. The molecular binding energy (MBE) results demonstrated that the MBE value of the flavonoids/aromatics, obtained from their binding with the COX2 protein, was lower than that obtained from their binding with the substrate, metabolism of arachidonic acid, whereas the MBE value of the aliphatics/terpenoids, obtained from their binding with the COX2 protein, was higher than that obtained from their binding with the substrate, arachidonic acid. Finally, further filtration, based on the physicochemical properties and the molecular binding energies of the small molecules, was carried out. Fortytwo natural GC components, including 35 flavonoid and 7 aromatic constituents, with low binding energies and potential inhibitory effects on COX2, were screened. Conclusion: Using the threestep program, pharmacophore screening, molecular docking, and physicochemical properties analysis, we screened out 35 flavonoid molecules and 7 aromatic molecules, which may be potential COX2 inhibitors, from GC. Two of the 35 flavonoid molecules (licochalcone A and glabridin) have been confirmed in the laboratory to have inhibitory effects on COX2. Our findings provide a material basis for the development of nonsteroidal GC drugs.